In 1898, Patterson was commissioned by the Uganda Railway committee in London to oversee the construction of a railway bridge over the Tsavo River in present-day Kenya. He arrived at the site in March of that year.

Almost immediately after Patterson's arrival, lion attacks began to take place on the workforce, with the lions dragging men out of their tents at night and feeding on their victims. Despite the building of thorn barriers (bomas) around the camps, bonfires at night, and strict after-dark curfews, the attacks escalated dramatically, to the point where the bridge construction eventually ceased due to a fearful, mass departure by the workers. Along with the obvious financial consequences of the work stoppage, Patterson faced the challenge of maintaining his authority and even his personal safety at this remote site against the increasingly hostile and superstitious workers, many of whom were convinced that the lions were in fact evil spirits, come to punish those who worked at Tsavo, and that he was the cause of the misfortune because the attacks had coincided with his arrival.

The man-eating behaviour was considered highly unusual for lions and was eventually confirmed to be the work of a pair of rogue males, who were believed to be responsible for as many as 140 deaths. Railway records officially attribute only 28 worker deaths to the lions, but the predators were also reported to have killed a significant number of local people of which no official record was ever kept, which attributed to the railway's smaller record.[citation needed]

Various theories have been put forward to account for the lions' man-eating behaviour: poor burial practices, low populations of food source animals due to disease, etc. There was a slave trade route through the area, which contributed to a considerable number of abandoned bodies. Patterson reported seeing considerable instances of unburied human remains and open graves in the area, and it is believed that the lions (which, like most predators will readily scavenge for food) adapted to this abundant, accessible food supply and eventually turned to humans as their primary food source. One of the lion's skulls was found to have a badly abscessed canine tooth that could have hindered normal hunting behaviour.[citation needed] However, this hypothesis accounts for the behaviour of only one of the lions involved, and Patterson himself personally disclaimed it, saying he had damaged the tooth.[citation needed]

With his reputation, livelihood, and safety at stake, Patterson, an experienced tiger hunter from his military service in India, undertook an extensive effort to deal with the crisis. After months of attempts and near misses, he finally killed the first lion on the night of 9 December 1898 and the second one on the morning of 29 December (narrowly escaping death when the wounded animal charged him). The lions were maneless like many others in the Tsavo area, and both were exceptionally large. Each lion was over nine feet long from nose to tip of tail and required at least eight men to carry it back to the camp.[citation needed]

The second Tsavo lion – killed 29 December 1898

The workers and local people immediately declared Patterson a hero, and word of the event quickly spread far and wide, as evidenced by the subsequent telegrams of congratulations he received. Word of the incident was even mentioned in the House of Lords, by the Prime Minister Lord Salisbury.[citation needed]

With the man-eater threat finally eliminated, the workforce returned and the Tsavo railway bridge was completed on 7 February 1899. Although the rails were destroyed by German soldiers during the First World War, the stone foundations were left standing and the bridge was subsequently repaired.[3] The workers, who in earlier months had all but threatened to kill him, presented Patterson with a silver bowl in appreciation for the risks he had undertaken on their behalf, with the following inscription:

"SIR, – We, your Overseer, Timekeepers, Mistaris and Workmen, present you with this bowl as a token of our gratitude to you for your bravery in killing two-man-eating lions at great risk to your own life, thereby saving us from the fate of being devoured by these terrible monsters who nightly broke into our tents and took our fellow-workers from our side. In presenting you with this bowl, we all add our prayers for your long life, happiness and prosperity. We shall ever remain, Sir, Your grateful servants,

Baboo PURSHOTAM HURJEE PURMAR, Overseer and Clerk of Works, on behalf of your Workmen. Dated at Tsavo, January 30, 1899."[4]

Patterson considered the bowl to be his most highly prized and hardest won trophy.

In 1924, after speaking at the Field Museum of Natural History in Chicago, Illinois, Patterson agreed to sell the Tsavo lion skins and skulls to the museum for the then sizeable sum of $5,000. The lion skins were then stuffed and are now on permanent display along with the original skulls.[5] The reconstructed lions are actually smaller than their original size, due to their skins' having been originally trimmed for use as trophy rugs in Patterson's house.[citation needed]

In 1906, Patterson returned to the Tsavo area for a hunting trip. During the trip, he shot an eland, which he noted possessed different features from elands in Southern Africa, where the species was first recognized. On returning to England, Patterson had the head of the eland mounted, where it was seen by Richard Lydekker, a member of the faculty of the British Museum. Lydekker identified Patterson's trophy as a new subspecies of eland, which Lydekker named Taurotragus oryx pattersonianius.

While on a safari with Audley Blyth, a son of James Blyth, 1st Baron Blyth, and Blyth's wife Ethel, Patterson's reputation was tarnished by Blyth's death by a gunshot wound (possible suicide – exact circumstances unknown). Witnesses confirmed that Patterson was not in Blyth's tent when the shooting took place, and that it was in fact Blyth's wife who was with him at the time, as she was reported as having run screaming from the tent immediately following the shooting. Patterson had Blyth buried in the wilderness and then insisted on continuing the expedition instead of returning to the nearest post to report the incident.

Shortly after, in poor health, Patterson returned to England with Mrs Blyth amid rumours of murder and an affair. Although he was never officially charged or censured, this incident followed him for years after in British society and in the army. His case was raised in Parliament in April 1909.[6] The incident was referenced in the film The Macomber Affair (1947), which was based on Ernest Hemingway's The Short Happy Life of Francis Macomber (1936).

During his time in command of the Jewish Legion (which served with distinction in the Palestine Campaign), Patterson was forced to deal with extensive, ongoing anti-semitism toward his men from many of his superiors (as well as peers and subordinates), and more than once threatened to resign his commission to bring the inappropriate treatment of his men under scrutiny. He retired from the British Army in 1920 as a Lieutenant-Colonel (the same rank he held when the war started) after thirty-five years of service. It is generally accepted that much of the admiration and respect of his men (and modern-day supporters) is due to the fact that he essentially sacrificed any opportunity for promotion (and his military career in general) in his efforts to ensure his men were treated fairly. His last two books, With the Zionists at Gallipoli (1916) and With the Judaeans in the Palestine Campaign (1922) are based on his experiences during these times.

After his military career, Patterson continued his support of Zionism. He remained a strong advocate of justice for the Jewish people as an active member of the Bergson Group and a promoter of a Jewish army to fight the Nazis and to stop the Holocaust. He was a member of the Emergency Committee to Save the Jewish People of Europe. During the Second World War, while he was in America, the British government cut off his pension, arguing they had no way to securely transmit his funds to him.[citation needed] This left Patterson in severe financial difficulty. Just the same, he energetically continued working toward the establishment of a separate Jewish state in the Middle East, which became a reality with the statehood of Israel on 14 May 1948, less than a year after his death.

Patterson was close friends with many Zionist supporters and leaders, among them Ze'ev Jabotinsky and Benzion Netanyahu. According to Benzion's younger son Benjamin Netanyahu, who later became Prime Minister of Israel, Benzion named his first son, Yonatan Netanyahu, after Patterson.[12][13] Patterson attended Yonatan Netanyahu’s circumcision and gave him a silver cup engraved with the words "To my beloved godson Yonatan from Lt.-Col. John Henry Patterson".[14] Yonatan Netanyahu became the commander of the elite Israeli commando unit Sayeret Matkal and was killed during Operation Entebbe in 1976.

He married Frances Helena Gray in 1895. She, in 1890, had been one of the first women to take a law degree in the UK.[15] Their son Bryan Patterson (1909–79) became a palaeontologist at the Field Museum in Chicago.[16]

During the 1940s, Patterson and his wife, "Francie", lived in a modest home in La Jolla, California. Eventually, with his wife in need of regular medical care and his own health in decline, he took up residence at the home of his friend Marion Travis in Bel Air, California, where he eventually died in his sleep at seventy-nine years of age. His wife would pass away six weeks later in a San Diego nursing home. Both Patterson and his wife were cremated, and their ashes were interred at Angelus-Rosedale Cemetery, niche 952-OC in Los Angeles.

According to Patterson's grandson, Alan Patterson, one of his final wishes was that both he and his wife eventually be interred in Israel, ideally, with or close to the men he commanded during the First World War.[17] The Jewish American Society for Historic Preservation (JASHP), Alan Patterson, Canadian representative Todd Young, Beit HaGedudim, and the Moshav of Avihayil effort led by Ezekiel Sivak, began a coordinated effort to honour this request in 2010. With the assistance and support of the Israeli government and Prime Minister Benjamin Netanyahu, on 4 December 2014, the remains of Patterson and his wife, were re-interred in the Avihayil cemetery where some of the men he commanded are buried. Attending the ceremony were Prime Minister Netanyahu, members of his family, military and cabinet members of the Israeli government, the British Ambassador, the Irish Ambassador, Alan Patterson, Jerry Klinger of the Jewish American Society for Historic Preservation, Ezekiel Sivak of Avihayil, representatives and descendent family members of the Jewish Legion, Christians supporters of Israel, 350 guests and numerous other dignitaries.[18] Netanyahu said of Patterson during his speech at the interment ceremony, Patterson was the godfather of the modern Israel Defense Forces. He went on to say (Patterson) was a "great friend of our people, a great champion of Zionism and a great believer in the Jewish State and the Jewish people....I feel it is an obligation of our people, our State and mine personally to fulfil his testimony".[19][20][21][22]

^Patterson, J.H.(1907) The Man-Eaters of Tsavo. Macmillan. In the introduction to the Peter Hathaway Capstick Libray edition (1986: St. Martin's Press), Capstick writes, "As for the Tsavo Bridge? Alas, the German forces blew it to atoms during the East African Campaign, wasting all the terror, death, and horror that surrounded its creation in the first place."

^Baboo PURSHOTAM HURJEE PURMAR, Overseer and Clerk of Works, on behalf of your Workmen. Dated at Tsavo, January 30, 1899.

^A. T. Q. Stewart, The Ulster Crisis (1967), p. 122; Timothy Bowman, Carson's Army: The Ulster Volunteer Force, 1910-22 (2007), p. 60. Denis Brian's biography does not mention any involvement with the UVF, but is rather vague on this period of Patterson's life.